Corey Cavanaugh, DO, is an academic nephrologist at the Cleveland Clinic. 

Corey Cavanaugh, DO

is rapidly transitioning into what clinicians described as a “mechanism-first era,” as emerging targeted therapies reshape how nephrologists approach diagnosis, risk stratification, and long-term disease management.

To commemorate IgAN Awareness Day on May 14, 2026, 

 spoke with nephrologists about key evolving concepts in IgAN, including earlier diagnosis, dynamic treatment sequencing, and unresolved questions around biomarkers and remission.

Corey Cavanaugh, DO — Cleveland Clinic nephrologist

Abdallah Geara, MD — Associate Professor of Clinical Medicine, University of Pennsylvania

Edgar Lerma, MD — Clinical Professor of Medicine, University of Illinois Chicago

“We now are in what we call a mechanism-first era,” said Edgar Lerma, MD. “We’re not in a sequencing-consensus era anymore in IgAN.”

Earlier Diagnosis Remains a Major Missed Opportunity

Despite therapeutic advances, clinicians emphasized that earlier recognition of IgAN remains one of the most important unmet needs in practice.

“The early diagnosis is, I think, the most critical,” said Corey Cavanaugh, DO. “That does not necessarily involve a new drug. It doesn’t even involve necessarily a new lab test.”

Instead, clinicians pointed to missed opportunities in routine care, particularly among younger patients presenting with microscopic hematuria, hypertension, or subtle urinary abnormalities.

“We know that 75% of patients with IgA nephropathy, when they’re biopsied, already have established CKD stage 3,” Geara said. “So early diagnosis is something we still need to work on.”

Experts also highlighted the lack of standardized screening approaches, including limited use of urinalysis in routine preventive care.

“If we can get sooner access and just basic things like urinalysis, blood pressure checks, creatinine checks in young people, we can identify a lot of this very early,” Cavanaugh added.

Risk Stratification Becomes More Dynamic and Prognostic

Clinicians described a shift away from static staging toward trajectory-based risk assessment incorporating proteinuria, eGFR slope, histology, and treatment response.

“The old model is that you have IgAN and will monitor kidney function over time,” Lerma said. “The new model is what we call an evidence-driven stratification era.”

He added that treatment response itself is now increasingly prognostic.

“How the patient responds to therapy within 12 months is becoming part of their prognosis,” Lerma said.

Proteinuria remains a central marker in clinical decision-making, despite limitations.

“The most powerful prognostic clinical indicator is proteinuria,” Cavanaugh said. “Unfortunately, it’s not a true biomarker in the sense that it tells us exactly what IgA is doing.”

A key challenge, clinicians added, is disease heterogeneity.

Expanding Treatment Options Complicate Sequencing Decisions

The IgAN treatment landscape now includes RAAS blockade, SGLT2 inhibitors, endothelin receptor antagonists, corticosteroids, targeted-release budesonide, complement inhibitors, and APRIL-directed therapies.

“The cornerstone remains ACE or ARB RAAS inhibition,” Cavanaugh said. “But endothelin receptor antagonists are the new nephron-sparing therapy that is not immunosuppression.”

He noted these agents can reduce proteinuria by approximately 50%, describing this as clinically meaningful for long-term prognosis.

Still, clinicians acknowledged there is no consensus on sequencing.

“The major question is who gets what and when,” Cavanaugh said.

“My core belief right now is nobody knows the right answer,” another clinician added. “The tools we have are inadequate to tell us exactly what to choose and when.”

Most clinicians, experts said, are still using a stepwise escalation approach rather than combination “stacking” of therapies.

Despite rapid innovation, adoption of newer therapies has been slower than expected.

Lerma outlined “five buckets” driving delayed uptake: regulatory burden, skepticism about surrogate endpoints like proteinuria, infrastructure challenges, disease heterogeneity, and physician familiarity.

“Most clinicians view reduction in proteinuria as positive,” Lerma said. “But whether it translates to preventing end-stage kidney disease still has some gray area.”

Additional barriers include prior authorization requirements, REMS programs, and monitoring demands.

“Adoption usually lags evidence by around 3 to 7 years in chronic kidney disease,” Lerma said.

APRIL Inhibition and the Future of Precision Nephrology

APRIL-targeted therapies are among the most closely watched emerging treatments, designed to reduce production of galactose-deficient IgA1 earlier in the disease pathway.

“These agents target upstream B-cell activation and reduce production of galactose-deficient IgA1,” Cavanaugh said.

Lerma added that APRIL inhibition may ultimately become a foundational therapy.

“In this moment, 2026, APRIL inhibition is not an add-on yet in standard practice, but it is a future backbone candidate,” he said.

Questions remain around dual APRIL–BAFF blockade and whether broader immunologic suppression improves outcomes or increases risk.

Despite therapeutic progress, clinicians emphasized that IgAN still lacks validated biomarkers for remission or precise response prediction.

“There’s still no definition of remission that we all agree on,” Cavanaugh said.

He added that improved therapies may ultimately force the field to define these endpoints more clearly.

“That’s the beauty of these therapies,” he said. “They force the issue of defining remission because we can actually achieve it.”

While IgAN remains incurable, clinicians expressed cautious optimism.

“There’s no cure,” Cavanaugh said. “But maybe we’re approaching that.”

Editor’s Note: Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics. Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others. Lerma reports disclosures with Amgen, Astra Zeneca, Calliditas, Novo Nordisk, Travere, Opko, and Otsuka

Cavanaugh C. Routine urinalysis in IgA nephropathy and young adults. 

 https://www.hcplive.com/view/routine-urinalysis-iga-nephropathy-young-adults-corey-cavanaugh

Geara A. Stratifying risk and optimizing therapy in IgA nephropathy. 

 https://www.hcplive.com/view/stratifying-risk-optimizing-therapy-iga-nephropathy-abdallah-geara-md

Articles

IgA nephropathy management is shifting to a mechanism-first paradigm as pathway-targeted agents expand beyond supportive care. Earlier recognition through urinalysis, blood pressure, and creatinine screening—particularly in young adults with microscopic hematuria—remains a major gap, with many first biopsied at CKD stage 3. Risk assessment is moving from static staging to trajectory-based prognostication using proteinuria, eGFR slope, histology, and 12‑month treatment response. Sequencing is unsettled amid more options and delayed adoption driven by regulatory, endpoint, infrastructure, and familiarity barriers. APRIL inhibition is a leading future backbone candidate.

On IgAN Awareness Day, clinicians highlight earlier diagnosis, dynamic risk stratification, and emerging targeted therapies reshaping care.

IgAN Enters “Mechanism-First Era” Reframing Diagnosis, Treatment, and Remission

2 IgA Nephropathy Experts Explain Clues For Early Intervention and Diagnosis

Two experts in nephrology are emphasizing the importance of identifying early clinical signs of IgA nephropathy (IgAN), often described as a silent disease.

“Clinicians should pay close attention to hypertension—especially in younger patients—and microscopic hematuria, again particularly in younger individuals,” said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “This is largely a young person’s disease, and it can be easy to explain these findings away or attribute them to something other than IgA nephropathy, since they’re relatively nonspecific. That’s why it requires a high index of suspicion and an astute clinician, particularly among non-nephrologists. It can be very subtle.”

Since these early findings are often attributed to benign or transient causes, diagnosis can often wind up delayed. By the time a majority of patients are diagnosed with IgAN, 50% to 75% have already progressed to chronic kidney disease (CKD) stage 3. At this point, eGFR falls below 60 mL/min/1.73 m² and structural kidney damage becomes irreversible, underscoring a need for earlier intervention. 

IgAN’s symptoms can be clinically silent before they progress to worsened stages, including non-visible hematuria, proteinuria, impaired kidney function, or hypertension. In one recent analysis, approximately 60% of IgAN cases were detected incidentally through hematuria or proteinuria identified on routine urinalysis. As a result, clinicians must rely heavily on measurable markers to assess disease activity and progression risk, with proteinuria remaining one of the most important indicators of long-term outcomes.

“When it comes to prognostication, we have to integrate clinical markers—serum creatinine, proteinuria, and hypertension—with demographic factors, including age and ethnicity, as well as histologic markers,” said Abdallah Geara, MD, Associate Professor of Clinical Medicine at the University of Pennsylvania, in an interview with HCPLive. “Bringing these together allows us to create a risk assessment for each patient, which then guides the next step in treatment. As therapies continue to evolve, the treatment algorithm has changed quite a bit over the last few years and will likely keep evolving.”

As the IgAN treatment landscape is experiencing a therapeutic revolution, this approach to risk stratification is becoming increasingly important. With 5 recently approved agents across distinct mechanistic pathways, therapeutic options are no longer the primary limitation. Instead, the focus is shifting toward earlier identification and precise risk assessment to ensure these therapies are deployed at a stage when they can have the greatest impact.

Editor’s Note: Abdallah reports relevant disclosures with Amgen, GlaxoSmithKline, Novartis, and others. Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics.

Stoneman S, Teh JW, O’Shaughnessy MM. IgA nephropathy in adults. 

. Published online January 26, 2026. doi:10.1001/jama.2025.25020

Kidney Disease: Improving Global Outcomes (KDIGO) Glomerular Diseases Work Group. KDIGO 2021 clinical practice guideline for the management of glomerular diseases. 

. 2021;100(4S):S1-S276. doi:10.1016/j.kint.2021.05.021

Videos

Corey Cavanaugh, DO, and Abdallah Geara, MD, separately share their perspectives on the clinical clues for IgAN diagnosis, including hypertension and microscopic hematuria.

Who Gets What, When? Navigating Therapy Selection in IgA Nephropathy, With Corey Cavanaugh, DO

 has considerably expanded recently, clinicians continue to navigate how best to select and sequence these emerging therapies for their patients.

New breakthrough developments have brought treatment options well beyond traditional approaches, such as corticosteroids and supportive care, now encompassing complement inhibitors and APRIL/BAFF-targeting agents.

“On the immunosuppressive side, we still have corticosteroids, we still have targeted release… sort of the newer kids on the block, if you will, are the complement inhibitor… and then our anti April therapies that are numerous and rolling out. Those are the major ones we're fixating on,” ​​said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “The major question is, who gets what and when, and that still is… this is a matter of, just to be clear right off the bat, this is not necessarily evidence-based. This is all just opinion-based.”

2025 Kidney Disease: Improving Global Outcomes (KDIGO) 

updated IgAN guidelines marked a conceptual shift, recommending clinicians to initiate therapies targeting pathogenic IgA production simultaneously with those addressing the consequences of existing nephron loss, a dual-track approach departing from the traditional stepwise model. The guidelines also introduced a more stringent proteinuria target, with the goal of achieving <0.3 g/d.

 proteinuria and eGFR remain the only validated biomarkers 

to guide therapy selection in the continuously expanding therapeutic landscape. Combination regimens may offer additive benefits, but supporting evidence is still emerging, and there is no existing evidence-based framework for sequencing decisions yet.

Meaningful progress toward personalized therapy in IgAN will depend on identifying biomarkers which can guide which patients are most likely to benefit from complement inhibition, APRIL blockade, or targeted intestinal therapy with Nefecon.

“My personal preference is to avoid steroids as much as I can, whether it be targeted release or oral systemic corticosteroids. That's just my personal preference. When we have a steroid-sparing option, I'm going to choose it. Young people don't like steroids… like anyone else.”

Current evidence supports guideline recommendations to avoid corticosteroid therapy in those with an eGFR <30 mL/min/1.73 m² and the suggestion to exercise cautiously in individuals at high risk of developing corticosteroid-related side effects, such as those with diabetes mellitus, obesity, latent infections, active peptic ulceration, uncontrolled psychiatric illness, and severe osteoporosis.

Editor’s Note: Cavanaugh reports relevant disclosures with Otsuka Pharmaceutical Co, Novartis Pharmaceutical Corporation, Travere Therapeutics, and Vera Therapeutics.

Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). 

https://doi.org/10.1016/j.kint.2025.04.003

In a rapidly evolving therapeutic landscape, how can clinicians make decisions to personalize IgAN care?

Even Routine Urinalysis Can Reveal Hidden IgAN In Young Patients, With Corey Cavanaugh, DO

 often silent presentation, clinicians should remain vigilant for hypertension and microscopic hematuria during routine evaluations, particularly among younger adults.

“It's not unusual that patients get a life insurance policy evaluation and get screened for hematuria, or they're getting some sort of surgery and a pre-op evaluation. Clinicians should pay close attention to hypertension and microscopic hematuria, especially in young people. Of course, this is a young person's disease,” said Corey Cavanaugh, DO, an academic nephrologist at the Cleveland Clinic, in an interview with HCPLive. “It can be easy to talk away these things, or at least give them a reasonable explanation that isn't IgAN, because they're non-specific features, so it requires a high index of suspicion and an astute clinician for the non-nephrologist, especially.”

The majority of patients with IgAN present with non-visible hematuria, proteinuria, impaired kidney function, or hypertension, features often classified as silent symptoms. A recent study found that approximately 60% of IgAN cases were detected incidentally through hematuria or proteinuria on urinalysis.

Since many early symptoms are subtle, clinicians often rely on measurable markers to assess disease activity and progression risk. Among these, proteinuria remains one of the most important indicators for identifying patients at greater risk of disease progression and kidney failure.

“The most powerful prognostic clinical indicators are few, actually, but the most powerful one I tend to adhere to is still proteinuria,” said Cavanaugh.

Proteinuria often serves as a key trigger for further diagnostic evaluation. According to the 2025 

Kidney Disease: Improving Global Outcomes (KDIGO) Clinical Practice Guidelines for IgAN and IgA Vasculitis (IgAV)

, clinicians should perform a kidney biopsy to confirm diagnosis in patients with suspected IgAN and persistent proteinuria ≥0.5 g/day.

Early detection is increasingly important as the therapeutic landscape for IgAN expands. New targeted treatments, including selective corticosteroids, dual endothelin-angiotensin blockers, and emerging complement inhibitors, offer opportunities to slow disease progression and reduce proteinuria.

Stoneman S, Teh JW, O’Shaughnessy MM. IgA Nephropathy in Adults. JAMA. Published online January 26, 2026. doi:

Floege J, Barratt J, Cook HT, et al. Executive summary of the KDIGO 2025 Clinical Practice Guideline for the Management of Immunoglobulin A Nephropathy (IgAN) and Immunoglobulin A Vasculitis (IgAV). Kidney international. 2025;108(4):548-554. doi:

Even Routine Urinalysis Can Reveal Hidden IgA Nephropathy, Especially in Young Adults